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1.
Br J Pharmacol ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38982680

RESUMEN

BACKGROUND AND PURPOSE: Triple-negative breast cancer (TNBC) has a poor prognosis due to limited therapeutic options. Recent studies have shown that TNBC is highly dependent on mitochondrial oxidative phosphorylation. The aim of this study was to investigate the potential of coptisine, a novel compound that inhibits the complex I of the mitochondrial electron transport chain (ETC), as a treatment for TNBC. EXPERIMENTAL APPROACH: In this study, mitochondrial metabolism in TNBC was analysed by bioinformatics. In vitro and in vivo experiments (in mice) were conducted to evaluate the potential of coptisine as an ETC complex I-targeting therapeutic agent and to investigate the molecular mechanisms underlying coptisine-induced mitochondrial dysfunction. The therapeutic effect of coptisine was assessed in TNBC cells and xenograft mouse model. KEY RESULTS: We demonstrated that mitochondrial ETC I was responsible for this metabolic vulnerability in TNBC. Furthermore, a naturally occurring compound, coptisine, exhibited specific inhibitory activity against this complex I. Treatment with coptisine significantly inhibited mitochondrial functions, reprogrammed cellular metabolism, induced apoptosis and ultimately inhibited the proliferation of TNBC cells. Additionally, coptisine administration induced prominent growth inhibition that was dependent on the presence of a functional complex I in xenograft mouse models. CONCLUSION AND IMPLICATIONS: Altogether, these findings suggest the promising potential of coptisine as a potent ETC complex I inhibitor to target the metabolic vulnerability of TNBC.

2.
Int J Nanomedicine ; 19: 7015-7031, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39011387

RESUMEN

Purpose: The incidence of hepatocellular carcinoma (HCC) is continuously increasing, and the mortality rate remains high. Thus, more effective strategies are needed to improve the treatment of HCC. Methods: In this study, we report the use of a visualized glypican-3 (GPC3)-targeting nanodelivery system (named GC-NBs) in combination with sonodynamic therapy (SDT) to enhance the therapeutic efficacy for treating HCC. The obtained nanodelivery system could actively target hepatocellular carcinoma cells and achieve ultrasound imaging through phase changes into nanobubbles under low-intensity ultrasound irradiation. Meanwhile, the released chlorine e6 (Ce6) after the nanobubbles collapse could lead to the generation of reactive oxygen species (ROS) under ultrasound irradiation to induce SDT. Results: Both in vitro and in vivo experiments have shown that GC-NBs can accumulate in tumour areas and achieve sonodynamic antitumour therapy under the navigation action of glypican-3-antibody (GPC3-Ab). Furthermore, in vitro and in vivo experiments did not show significant biological toxicity of the nanodelivery system. Moreover, GC-NBs can be imaged with ultrasound, providing personalized treatment monitoring. Conclusion: GC-NBs enable a visualized antitumour strategy from a targeted sonodynamic perspective by combining tumour-specific targeting and stimuli-responsive controlled release into a single system.


Asunto(s)
Carcinoma Hepatocelular , Glipicanos , Neoplasias Hepáticas , Terapia por Ultrasonido , Glipicanos/metabolismo , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/tratamiento farmacológico , Animales , Humanos , Terapia por Ultrasonido/métodos , Ratones , Línea Celular Tumoral , Clorofilidas , Especies Reactivas de Oxígeno/metabolismo , Ratones Endogámicos BALB C , Células Hep G2 , Ratones Desnudos , Ensayos Antitumor por Modelo de Xenoinjerto , Ultrasonografía/métodos , Nanopartículas/química
3.
Phytochem Anal ; 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38924240

RESUMEN

INTRODUCTION: The identification of active dietary flavonoids in food is promising for novel drug discovery. The active ingredients of duckweed (a widely recognized food and herb with abundant flavonoids) that are associated with acute myeloid leukemia (AML) have yet to be identified, and their underlying mechanisms have not been elucidated. OBJECTIVES: The objective of this study was to identify novel constituents exhibiting antileukemia activity in duckweed through the integration of chemical profiling, network pharmacology, and experimental validation. METHODS: First, high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to characterize the primary constituents of duckweed. Subsequently, AML cell-xenograft tumor models were used to validate the anticancer effect of duckweed extract. Furthermore, network pharmacology analysis was conducted to predict the potential active compounds and drug targets against AML. Lastly, based on these findings, two monomers (apiin and luteoloside) were selected for experimental validation. RESULTS: A total of 17 compounds, all of which are apigenin and luteolin derivatives, were identified in duckweed. The duckweed extract significantly inhibited AML cell growth in vivo. Furthermore, a total of 88 targets for duckweed against AML were predicted, with key targets including PTGS2, MYC, MDM2, VEGFA, CTNNB1, CASP3, EGFR, TP53, HSP90AA1, CCND1, MMP9, TNF, and MAPK1. GO and KEGG pathway enrichment analyses indicated that these targets were primarily involved in the apoptotic signaling pathway. Lastly, both apiin and luteoloside effectively induced apoptosis through CASP3 activation, and this effect could be partially reversed by a caspase inhibitor (Z-VAD). CONCLUSION: Duckweed extract has an antileukemic effect, and apiin derived from duckweed shows potential as a treatment for AML.

4.
FASEB J ; 38(13): e23706, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38877842

RESUMEN

The etiology of preeclampsia (PE), a complex and multifactorial condition, remains incompletely understood. DNA methylation, which is primarily regulated by three DNA methyltransferases (DNMTs), DNMT1, DNMT3A, and DNMT3B, plays a vital role in early embryonic development and trophectoderm differentiation. Yet, how DNMTs modulate trophoblast fusion and PE development remains unclear. In this study, we found that the DNMTs expression was downregulated during trophoblast cells fusion. Downregulation of DNMTs was observed during the reconstruction of the denuded syncytiotrophoblast (STB) layer of placental explants. Additionally, overexpression of DNMTs inhibited trophoblast fusion. Conversely, treatment with the DNA methylation inhibitor 5-aza-CdR decreased the expression of DNMTs and promoted trophoblast fusion. A combined analysis of DNA methylation data and gene transcriptome data obtained from the primary cytotrophoblasts (CTBs) fusion process identified 104 potential methylation-regulated differentially expressed genes (MeDEGs) with upregulated expression due to DNA demethylation, including CD59, TNFAIP3, SDC1, and CDK6. The transcription regulation region (TRR) of TNFAIP3 showed a hypomethylation with induction of 5-aza-CdR, which facilitated CREB recruitment and thereby participated in regulating trophoblast fusion. More importantly, clinical correlation analysis of PE showed that the abnormal increase in DNMTs may be involved in the development of PE. This study identified placental DNA methylation-regulated genes that may contribute to PE, offering a novel perspective on the role of epigenetics in trophoblast fusion and its implication in PE development.


Asunto(s)
ADN (Citosina-5-)-Metiltransferasas , Metilación de ADN , Preeclampsia , Trofoblastos , Trofoblastos/metabolismo , Femenino , Preeclampsia/genética , Preeclampsia/metabolismo , Preeclampsia/patología , Embarazo , Humanos , ADN (Citosina-5-)-Metiltransferasas/genética , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Fusión Celular , Placenta/metabolismo , ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , ADN (Citosina-5-)-Metiltransferasa 1/genética
5.
J Clin Nurs ; 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38873868

RESUMEN

AIM AND OBJECTIVE: This study aims to scrutinize the interconnected concepts, prevailing landscape and efficacy of personalized nursing within the framework of blockchain technology and to proffer a roadmap for prospective scholarly inquiries. BACKGROUND: The ethos of personalized nursing as a paradigm grounded in human-centered care has been venerated as the pinnacle of nursing practice. Recent years have witnessed the emergence of groundbreaking technologies, notably blockchain, which have set the stage for the actualization of personalized nursing care. Nevertheless, a lacuna persists in the holistic comprehension surrounding the integration of blockchain technology within the domain of personalized nursing. DESIGN AND METHODS: We considered studies published in English from 2018 to the present. Databases searched included CINAHL, Pubmed, MEDLINE, Scopus. Sources of grey literature that were searched included ProQuest Dissertations and Theses. The eligibility of the studies was independently appraised by a pair of researchers. The findings are delineated through narratives and tabular presentations. RESULTS: The narrative findings are stratified into three primary domains: (1) the theoretical underpinnings of personalized nursing vis-à-vis the integration of blockchain technology; (2) delineation of the specific domains within nursing where blockchain applications are germane to personalized nursing; and (3) the demonstrable impact of blockchain technology on the efficacy of personalized nursing. CONCLUSION: Blockchain technology has wrought profound transformations in the landscape of personalized nursing. As blockchain technology continues to evolve, future scholarship necessitates elucidation on the conceptual intricacies of personalized nursing interfaced with blockchain technology, and broadening of the research purview to encompass a comprehensive understanding of the various applications of personalized nursing. REPORTING METHOD: This scoping review adhered to relevant EQUATOR guidelines and used the PRISMA-ScR.

6.
Artículo en Inglés | MEDLINE | ID: mdl-38695864

RESUMEN

A novel actinobacterium, designated strain CWNU-1T, was isolated from the rhizospheric soil of Fritillaria cirrhosa D. Don and examined using a polyphasic taxonomic approach. The organism developed pale blue aerial mycelia that was simply branched and terminated in open or closed coils of three or more volutions on International Streptomyces Project 3 agar. Spores were ellipsoidal to cylindrical with wrinkled surfaces. The strain showed high 16S rRNA gene sequence similarity to Streptomyces kurssanovii NBRC 13192T (98.8 %), Streptomyces xantholiticus NBRC 13354T (98.7 %) and Streptomyces peucetius JCM 9920T (98.6 %). The phylogenetic result based on 16S rRNA gene and genome sequences clearly demonstrated that strain CWNU-1T formed an independent phylogenetic lineage. On the basis of orthologous average nucleotide identity, CWNU-1T was most closely related to Streptomyces inusitatus NBRC 13601T with 79.3 % identity. The results of the digital DNA-DNA hybridization analysis also indicated low levels of relatedness with other species, as the highest value was observed with S. inusitatus NBRC 13601T (25.3 %). With reference to phenotypic characteristics, phylogenetic data, orthologous average nucleotide identity and digital DNA-DNA hybridization results, strain CWNU-1T was readily distinguished from its most closely related strains and classified as representing a novel species, for which the name Streptomyces albipurpureus sp. nov. is proposed. The type strain is CWNU-1T (=CGMCC 4.7758T=MCCC 1K07402T=JCM 35391T).


Asunto(s)
Técnicas de Tipificación Bacteriana , Composición de Base , ADN Bacteriano , Ácidos Grasos , Fritillaria , Hibridación de Ácido Nucleico , Filogenia , ARN Ribosómico 16S , Rizosfera , Análisis de Secuencia de ADN , Microbiología del Suelo , Streptomyces , Streptomyces/genética , Streptomyces/clasificación , Streptomyces/aislamiento & purificación , ARN Ribosómico 16S/genética , ADN Bacteriano/genética , Ácidos Grasos/análisis , Fritillaria/microbiología , Vitamina K 2/análogos & derivados
7.
Org Biomol Chem ; 22(19): 3986-3994, 2024 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-38695061

RESUMEN

Algae-based marine carbohydrate drugs are typically decorated with negative ion groups such as carboxylate and sulfate groups. However, the precise synthesis of highly sulfated alginates is challenging, thus impeding their structure-activity relationship studies. Herein we achieve a microwave-assisted synthesis of a range of highly sulfated mannuronate glycans with up to 17 sulfation sites by overcoming the incomplete sulfation due to the electrostatic repulsion of crowded polyanionic groups. Although the partially sulfated tetrasaccharide had the highest affinity for the receptor binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, the fully sulfated octasaccharide showed the most potent interference with the binding of the RBD to angiotensin-converting enzyme 2 (ACE2) and Vero E6 cells, indicating that the sulfated oligosaccharides might inhibit the RBD binding to ACE2 in a length-dependent manner.


Asunto(s)
Enzima Convertidora de Angiotensina 2 , Antivirales , Microondas , Polisacáridos , SARS-CoV-2 , SARS-CoV-2/efectos de los fármacos , Antivirales/farmacología , Antivirales/síntesis química , Antivirales/química , Chlorocebus aethiops , Enzima Convertidora de Angiotensina 2/metabolismo , Enzima Convertidora de Angiotensina 2/antagonistas & inhibidores , Enzima Convertidora de Angiotensina 2/química , Células Vero , Polisacáridos/química , Polisacáridos/farmacología , Polisacáridos/síntesis química , Humanos , Animales , Glicoproteína de la Espiga del Coronavirus/antagonistas & inhibidores , Glicoproteína de la Espiga del Coronavirus/metabolismo , Glicoproteína de la Espiga del Coronavirus/química , Ácidos Hexurónicos/química , Ácidos Hexurónicos/farmacología , Ácidos Hexurónicos/síntesis química , Sulfatos/química , Sulfatos/farmacología , Sulfatos/síntesis química , Tratamiento Farmacológico de COVID-19 , Relación Estructura-Actividad
8.
Cell Death Dis ; 15(5): 356, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38778059

RESUMEN

IL-33 is a danger signal that binds to its receptor ST2L to promote tumor progression. This study identifies the IL-33/ST2L positive-feedback loop and the trafficking of ST2L membrane presentation in macrophages that contribute to lung tumor progression. Mechanistically, IL-33 induces ST2L upregulation by activating NF-κB, which binds to the promoter region of the ST2L gene. Moreover, Rab37, a small GTPase involved in membrane trafficking, mediates ST2L trafficking to the plasma membrane of M2 macrophages. This IL-33/NF-κB/ST2L/Rab37 axis promotes positive-feedback loops that enhance ST2L expression and membrane trafficking in M2 macrophages. Notably, neutralizing antibodies against IL-33 or ST2L block NF-κB activity, suppress M2 macrophage polarization, and synergistically inhibit tumor growth when combined with cisplatin treatment in vitro/vivo. Clinically, Rab37+/ST2L+/CD206+ tumor-infiltrating M2 macrophages correlate with advanced-stage lung cancer patients with poor response to chemotherapy. These findings unveil a positive-feedback mechanism and provide a basis for IL-33/ST2L-targeting therapy for cancer.


Asunto(s)
Interleucina-33 , Neoplasias Pulmonares , Macrófagos , FN-kappa B , Proteínas de Unión al GTP rab , Interleucina-33/metabolismo , Interleucina-33/genética , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , FN-kappa B/metabolismo , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Animales , Proteínas de Unión al GTP rab/metabolismo , Proteínas de Unión al GTP rab/genética , Ratones , Retroalimentación Fisiológica , Línea Celular Tumoral , Transducción de Señal/efectos de los fármacos , Ratones Endogámicos C57BL , Femenino
9.
Pharmacol Biochem Behav ; 239: 173775, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38657873

RESUMEN

Electroconvulsive shock (ECS) is utilized to treat depression but may cause learning/memory impairments, which may be ameliorated by anesthetics through the modulation of hippocampal synaptic plasticity. Given that synaptic plasticity is governed by aerobic glycolysis, it remains unclear whether anesthetics modulate aerobic glycolysis to enhance learning and memory function. Depression-like behavior in rats was induced by chronic mild unpredictable stress (CUMS), with anhedonia assessed via sucrose preference test (SPT). Depressive-like behaviors and spatial learning/memory were assessed with forced swim test (FST), open field test (OFT), and Morris water maze (MWM) test. Changes in aerobic glycolysis and synaptic plasticity in the hippocampal region of depressive-like rats post-ECS were documented using immunofluorescence analysis, Western blot, Lactate Assay Kit and transmission electron microscopy. Both the OFT and FST indicated that ECS was effective in alleviating depressive-like behaviors. The MWM test demonstrated that anesthetics were capable of attenuating ECS-induced learning and memory deficits. Immunofluorescence analysis, Western blot, Lactate Assay Kit and transmission electron microscopy revealed that the decline in learning and memory abilities in ECS-induced depressive-like rats was correlated with decreased aerobic glycolysis, and that the additional use of ciprofol or propofol ameliorated these alterations. Adding the glycolysis inhibitor 2-DG diminished the ameliorative effects of the anesthetic. No significant difference was observed between ciprofol and propofol in enhancing aerobic glycolysis in astrocytes and synaptic plasticity after ECS. These findings may contribute to understanding the mechanisms by which anesthetic drugs modulate learning and memory impairment after ECS in depressive-like behavior rats.


Asunto(s)
Depresión , Glucólisis , Hipocampo , Trastornos de la Memoria , Ratas Sprague-Dawley , Animales , Ratas , Masculino , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Glucólisis/efectos de los fármacos , Depresión/metabolismo , Depresión/tratamiento farmacológico , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/tratamiento farmacológico , Plasticidad Neuronal/efectos de los fármacos , Electrochoque , Estrés Psicológico/metabolismo , Estrés Psicológico/tratamiento farmacológico , Modelos Animales de Enfermedad , Propofol/farmacología , Aprendizaje por Laberinto/efectos de los fármacos
10.
Opt Express ; 32(7): 11346-11362, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38570984

RESUMEN

An open challenge remained in designing an optical system to capture the aerial image with a wide field of view (FoV) and high resolution. The optical system of one camera from a single unmanned aerial vehicle (UAV) can hardly promise the FoV and resolution. The conventional swarm UAVs can form the camera array with a short or fixed baseline. They can capture the images with a wide FoV and high resolution, but the cost is the requirement of many UAVs. We aim to design a camera array with a wide and dynamic baseline to reduce the demand for UAVs to organize a synthetic optical aperture. In this thought, we propose a master-slave UAVs-based synthetic optical aperture imaging system with a wide and dynamic baseline. The system consists of one master UAV and multiple slave UAVs. Master and slave UAVs provide the global and local FoVs, respectively, and improve the efficiency of image acquisition. In such a system, fusing UAV images becomes a new challenge due to two factors: (i) the small FoV overlap of slave UAVs and (ii) the gap in resolution scale from slave to master UAV images. To deal with it, a coarse-to-fine stitching method is proposed to stitch up the multi-view images into one to obtain a wide FoV with high resolution. A video stabilization method has also been designed for the proposed imaging system. Challenges caused by wide and dynamic baselines can thus be solved by the above methods. Actual data experiments demonstrate that the proposed imaging system achieves high-quality imaging results.

11.
Life Sci ; 342: 122513, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38387700

RESUMEN

BACKGROUND: The epidermic microbiota plays crucial roles in the pathogenesis of atopic dermatitis (AD), a common inflammatory skin disease. Melatonin (MLT) has been shown to ameliorate skin damage in AD patients, yet the underlying mechanism is unclear. METHODS: Using 2,4-dinitrofluorobenzene (DNFB) to induce an AD model, MLT intervention was applied for 14 days to observe its pharmaceutical effect. Skin lesions were observed using HE staining, toluidine blue staining and electron microscopy. Dermal proinflammatory factor (IL-4 and IL-13) and intestinal barrier indices (ZO1 and Occludin) were assessed by immunohistochemistry and RT-qPCR, respectively. The dysbiotic microbiota was analyzed using 16S rRNA sequencing. RESULTS: MLT significantly improved skin lesion size; inflammatory status (mast cells, IgE, IL-4, and IL-13); and the imbalance of the epidermal microbiota in AD mice. Notably, Staphylococcus aureus is the key bacterium associated with dysbiosis of the epidermal microbiota and may be involved in the fine modulation of mast cells, IL-4, IL-13 and IgE. Correlation analysis between AD and the gut revealed that intestinal dysbiosis occurred earlier than that of the pathological structure in the gut. CONCLUSION: Melatonin reverses DNFB-induced skin damage and epidermal dysbiosis, especially in S. aureus.


Asunto(s)
Dermatitis Atópica , Melatonina , Microbiota , Enfermedades de la Piel , Humanos , Ratones , Animales , Dermatitis Atópica/inducido químicamente , Dermatitis Atópica/tratamiento farmacológico , Dinitrofluorobenceno/toxicidad , Melatonina/farmacología , Interleucina-13 , Staphylococcus aureus , Interleucina-4/farmacología , ARN Ribosómico 16S/genética , Disbiosis/patología , Piel , Enfermedades de la Piel/patología , Inmunoglobulina E
12.
Org Biomol Chem ; 22(12): 2365-2369, 2024 03 20.
Artículo en Inglés | MEDLINE | ID: mdl-38416050

RESUMEN

A DMF-modulated glycosylation approach for the stereoselective synthesis of α-Kdo glycosides with readily accessible peracetylated Kdo ynenoate as a donor was described. By utilizing this approach, we completed the synthesis of various linkage types of Kdo-Kdo disaccharides and the α-Kdo-containing protected trisaccharide variant relevant to the lipopolysaccharide of Coxiella burnetii strain Nine Mile.


Asunto(s)
Glicósidos , Lipopolisacáridos , Glicosilación , Disacáridos , Trisacáridos
13.
Opt Lett ; 49(3): 562-565, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38300059

RESUMEN

Multifocal multiview (MFMV) is an emerging high-dimensional optical data that allows to record richer scene information but yields huge volumes of data. To unveil its imaging mechanism, we present an angular-focal-spatial representation model, which decomposes high-dimensional MFMV data into angular, spatial, and focal dimensions. To construct a comprehensive MFMV dataset, we leverage representative imaging prototypes, including digital camera imaging, emerging plenoptic refocusing, and synthesized Blender 3D creation. It is believed to be the first-of-its-kind MFMV dataset in multiple acquisition ways. To efficiently compress MFMV data, we propose the first, to our knowledge, MFMV data compression scheme based on angular-focal-spatial representation. It exploits inter-view, inter-stack, and intra-frame predictions to eliminate data redundancy in angular, focal, and spatial dimensions, respectively. Experiments demonstrate the proposed scheme outperforms the standard HEVC and MV-HEVC coding methods. As high as 3.693 dB PSNR gains and 64.22% bitrate savings can be achieved.

14.
BMC Complement Med Ther ; 24(1): 21, 2024 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-38178115

RESUMEN

BACKGROUND: This study aims to assess the efficacy and safety of Qingpeng ointment (QPO), a Tibetan medicine for alleviating symptoms in individuals with acute gouty arthritis (AGA). METHODS: This study was a randomized, double-blind, placebo-controlled trial that involved individuals with AGA whose joint pain, as measured on a visual analog scale (VAS) from 0 to 10, was equal to or greater than 3. The participants were randomly assigned to either the QPO or the placebo group and received their respective treatments twice daily for seven consecutive days. In case of intolerable pain, the participants were allowed to use diclofenac sodium sustained-release tablets as a rescue medicine. The primary outcomes measured were joint pain and swelling, while the secondary outcomes included joint mobility, redness, serum uric acid levels, C-reactive protein levels, and the amount of remaining rescue medicine. Any adverse events that occurred during the trial were also recorded. RESULTS: A total of 203 cases were divided into two groups, with balanced baselines: 102 in the QPO group and 101 in the placebo group. For joint pain, differences between the groups were notable in the VAS scores [1.75 (0, 3.00) versus 2.00 (1.00, 3.50); P = 0.038], changes in VAS [5.00 (3.00, 6.00) versus 4.00 (2.00, 6.00); P = 0.036], and disappearance rate [26.47% compared to 15.84%; P = 0.046] after treatment. Concerning joint swelling, significant between-group differences were observed in the VAS scores [1.00 (0, 2.30) versus 2.00 (0.70, 3.00); P = 0.032] and disappearance rate [33.33% compared to 21.78%; P = 0.046] at treatment completion. The QPO group exhibited a statistically significant mobility improvement compared to the placebo group (P = 0.004). No significant differences were found in other secondary outcomes. Five patients, four from the QPO group and one from the other, encountered mild adverse events, primarily skin irritation. All of these cases were resolved after dosage reduction or discontinuation of the medication. CONCLUSIONS: Compared to the placebo, QPO exhibits positive effects on AGA by alleviating pain, reducing swelling, and enhancing joint mobility, without causing significant adverse effects. TRIAL REGISTRATION: ISRCTN34355813. Registered on 25/01/2021.


Asunto(s)
Artritis Gotosa , Humanos , Artritis Gotosa/tratamiento farmacológico , Pomadas/uso terapéutico , Medicina Tradicional Tibetana/efectos adversos , Ácido Úrico , Dolor/tratamiento farmacológico , Artralgia
15.
Biomater Sci ; 12(5): 1281-1293, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38252410

RESUMEN

Acute liver injury (ALI) is a highly fatal condition characterized by sudden massive necrosis of liver cells, inflammation, and impaired coagulation function. Currently, the primary clinical approach for managing ALI involves symptom management based on the underlying causes. The association between excessive reactive oxygen species originating from macrophages and acute liver injury is noteworthy. Therefore, we designed a novel nanoscale phase variant contrast agent, denoted as PFP@CeO2@Lips, which effectively scavenges reactive oxygen species, and enables visualization through low intensity pulsed ultrasound activation. The efficacy of the nanoparticles in scavenging excess reactive oxygen species from RAW264.7 and protective AML12 cells has been demonstrated through in vitro and in vivo experiments. Additionally, these nanoparticles have shown a protective effect against LPS/D-GalN attack in C57BL/6J mice. Furthermore, when exposed to LIPUS irritation, the nanoparticles undergo liquid-gas phase transition and enable ultrasound imaging.


Asunto(s)
Hígado , Nanopartículas , Ratones , Animales , Especies Reactivas de Oxígeno , Ratones Endogámicos C57BL , Hígado/diagnóstico por imagen , Inflamación , Ondas Ultrasónicas
16.
Poult Sci ; 103(1): 103247, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37980731

RESUMEN

The mitochondrial quality control system is crucial in maintaining cellular homeostasis during environmental stress. Granulosa cells are the main cells secreting steroid hormones, and mitochondria are the key organelles for steroid hormone synthesis. The impact of the mitochondrial quality control system on granulosa cells' steroid hormone synthesis and survival under heat stress is still unclear. Here, we showed that acute heat stress induces mitochondrial damage and significantly increases the number of mitophagy-like vesicles in the cytoplasm of duck ovary granulosa cells at the ultra-structural level. Meanwhile, we also found heat stress significantly increased mitochondrial fission and mitophagy-related protein expression levels both in vivo and in vitro. Furthermore, by confocal fluorescence analysis, we discovered that LC3 was distributed spot-like manner near the nucleus in the heat treatment group, and the LC3 spots and lysosomes were colocalized with Mito-Tracker in the heat treatment group. We further detected the mitophagy-related protein in the cytoplasm and mitochondria, respectively. Results showed that the PINK1 protein was significantly increased both in cytoplasm and mitochondria, while the LC3-Ⅱ/LC3-Ⅰ ratio increase only occurred in mitochondrial. In addition, the autophagy protein induced by acute heat treatment was effectively inhibited by the mitophagy inhibitor CysA. Finally, we demonstrated that the alteration of cellular mitophagy by siRNA interference with Drp1 and PINK1 inhibited the steroid synthesis of granulosa cells and increased cell apoptosis. Study provides strong evidence that the Drp1 regulated PINK1-dependent mitophagy pathway protects follicular granulosa cells from acute heat stress-induced injury.


Asunto(s)
Patos , Mitofagia , Femenino , Animales , Patos/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/farmacología , Pollos/metabolismo , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , Células de la Granulosa/metabolismo , Hormonas , Respuesta al Choque Térmico , Esteroides/farmacología
17.
J Extracell Vesicles ; 13(1): e12397, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38158550

RESUMEN

Cerebrospinal fluid (CSF) is a clear, transparent fluid derived from blood plasma that protects the brain and spinal cord against mechanical shock, provides buoyancy, clears metabolic waste and transports extracellular components to remote sites in the brain. Given its contact with the brain and the spinal cord, CSF is the most informative biofluid for studies of the central nervous system (CNS). In addition to other components, CSF contains extracellular vesicles (EVs) that carry bioactive cargoes (e.g., lipids, nucleic acids, proteins), and that can have biological functions within and beyond the CNS. Thus, CSF EVs likely serve as both mediators of and contributors to communication in the CNS. Accordingly, their potential as biomarkers for CNS diseases has stimulated much excitement for and attention to CSF EV research. However, studies on CSF EVs present unique challenges relative to EV studies in other biofluids, including the invasive nature of CSF collection, limited CSF volumes and the low numbers of EVs in CSF as compared to plasma. Here, the objectives of the International Society for Extracellular Vesicles CSF Task Force are to promote the reproducibility of CSF EV studies by providing current reporting and best practices, and recommendations and reporting guidelines, for CSF EV studies. To accomplish this, we created and distributed a world-wide survey to ISEV members to assess methods considered 'best practices' for CSF EVs, then performed a detailed literature review for CSF EV publications that was used to curate methods and resources. Based on responses to the survey and curated information from publications, the CSF Task Force herein provides recommendations and reporting guidelines to promote the reproducibility of CSF EV studies in seven domains: (i) CSF Collection, Processing, and Storage; (ii) CSF EV Separation/Concentration; (iii) CSF EV Size and Number Measurements; (iv) CSF EV Protein Studies; (v) CSF EV RNA Studies; (vi) CSF EV Omics Studies and (vii) CSF EV Functional Studies.


Asunto(s)
Vesículas Extracelulares , Biomarcadores/metabolismo , Encéfalo/metabolismo , Vesículas Extracelulares/metabolismo , Proteínas/metabolismo , Reproducibilidad de los Resultados
18.
Opt Express ; 31(24): 39483-39499, 2023 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-38041269

RESUMEN

Varifocal multiview (VFMV) is an emerging high-dimensional optical data in computational imaging and displays. It describes scenes in angular, spatial, and focal dimensions, whose complex imaging conditions involve dense viewpoints, high spatial resolutions, and variable focal planes, resulting in difficulties in data compression. In this paper, we propose an efficient VFMV compression scheme based on view mountain-shape rearrangement (VMSR) and all-directional prediction structure (ADPS). The VMSR rearranges the irregular VFMV to form a new regular VFMV with mountain-shape focusing distributions. This special rearrangement features prominently in enhancing inter-view correlations by smoothing focusing status changes and moderating view displacements. Then, the ADPS efficiently compresses the rearranged VFMV by exploiting the enhanced correlations. It conducts row-wise hierarchy divisions and creates prediction dependencies among views. The closest adjacent views from all directions serve as reference frames to improve the prediction efficiency. Extensive experiments demonstrate the proposed scheme outperforms comparison schemes by quantitative, qualitative, complexity, and forgery protection evaluations. As high as 3.17 dB gains of peak signal-to-noise ratio (PSNR) and 61.1% bitrate savings can be obtained, achieving the state-of-the-art compression performance. VFMV is also validated could serve as a novel secure imaging format protecting optical data against the forgery of large models.

19.
Ann Hematol ; 2023 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-38148344

RESUMEN

The E2A-PBX1 gene fusion is a common translocation in B-cell acute lymphoblastic leukaemia. Patients harbouring the E2A-PBX1 fusion gene typically exhibit an intermediate prognosis. Furthermore, minimal residual disease has unsatisfactory prognostic value in E2A-PBX1 B-cell acute lymphoblastic leukaemia. However, the mechanism of E2A-PBX1 in the occurrence and progression of B-cell acute lymphoblastic leukaemia is not well understood. Here, we mainly review the roles of E2A and PBX1 in the differentiation and development of B lymphocytes, the mechanism of E2A-PBX1 gene fusion in B-cell acute lymphoblastic leukaemia, and the potential therapeutic approaches.

20.
Diagnostics (Basel) ; 13(21)2023 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-37958276

RESUMEN

BACKGROUND: Machine-learning (ML) and radiomics features have been utilized for survival outcome analysis in various cancers. This study aims to investigate the application of ML based on patients' clinical features and radiomics features derived from bone scintigraphy (BS) and to evaluate recurrence-free survival in local or locally advanced prostate cancer (PCa) patients after the initial treatment. METHODS: A total of 354 patients who met the eligibility criteria were analyzed and used to train the model. Clinical information and radiomics features of BS were obtained. Survival-related clinical features and radiomics features were included in the ML model training. Using the pyradiomics software, 128 radiomics features from each BS image's region of interest, validated by experts, were extracted. Four textural matrices were also calculated: GLCM, NGLDM, GLRLM, and GLSZM. Five training models (Logistic Regression, Naive Bayes, Random Forest, Support Vector Classification, and XGBoost) were applied using K-fold cross-validation. Recurrence was defined as either a rise in PSA levels, radiographic progression, or death. To assess the classifier's effectiveness, the ROC curve area and confusion matrix were employed. RESULTS: Of the 354 patients, 101 patients were categorized into the recurrence group with more advanced disease status compared to the non-recurrence group. Key clinical features including tumor stage, radical prostatectomy, initial PSA, Gleason Score primary pattern, and radiotherapy were used for model training. Random Forest (RF) was the best-performing model, with a sensitivity of 0.81, specificity of 0.87, and accuracy of 0.85. The ROC curve analysis showed that predictions from RF outperformed predictions from other ML models with a final AUC of 0.94 and a p-value of <0.001. The other models had accuracy ranges from 0.52 to 0.78 and AUC ranges from 0.67 to 0.84. CONCLUSIONS: The study showed that ML based on clinical features and radiomics features of BS improves the prediction of PCa recurrence after initial treatment. These findings highlight the added value of ML techniques for risk classification in PCa based on clinical features and radiomics features of BS.

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